This invention relates to the use of certain 4-phenylpiperidines in the treatment of pruritus, including allergic dermatitis and atopy, in animals and humans.
Itching or pruritus is a common dermatological symptom which can give rise to considerable distress, in both humans and animals. Pruritus is often associated with inflammatory skin disease which can commonly be caused by hypersensitivity reactions (such as reaction to insect bites e.g. flea bites, or to environmental allergens such as house dust mite or pollen), bacterial and fungal infections of the skin or ectoparasite infections. Previous treatments for pruritus include the use of corticosteroids and antihistamines, however both have undesired side effects. Other therapies include the use of essential fatty acid dietary supplements which are slow to act and offer only limited efficacy against allergic dermatitis.
WO84/00889 and U.S. Pat. No. 4,181,726 disclose the use of the opioid antagonist naloxone in the treatment of pruritus, however naloxone has not been commercially exploited for the control of pruritus, and there is a continuing need for a cheap and effective remedy.
Certain 1,3,4-trisubstituted 4-aryl-piperidine derivatives are disclosed in GB-A-1525584 as potent narcotic antagonists which also display analgesic properties. These compounds are also claimed in EP-A-0287339 as opioid antagonists which block the effect of agonists at the mu or kappa receptors, having potential utility in treating a variety of disorders associated with these receptors such as eating disorders, opiate overdose, depression, smoking, alcoholism, sexual dysfunction, shock, stroke, spinal damage and head trauma. The structure activity relationships of this series of compounds is reviewed in J. Medicinal Chemistry, 1993, 36, 2833 and their effect on food consumption in obese Zuker rats is described in J. Medicinal Chemistry 1993, 36, 2842. Potential utility is suggested as an appetite suppressant for weight loss. Further related 1-N-substituted-4-aryl piperidines are disclosed as peripherally selective opioid antagonists in EP-A-0506468 and EP-A-0506478. Potential utility is suggested in preventing peripherally mediated undesired opiate effects and in relieving the symptoms of idiopathic constipation and irritable bowel syndrome. We have now unexpectedly discovered that such compounds also have activity as antipruritic agents.